Mammary tumorigenesis induced by exogenous infection with MMTV is accompanied by integration of viral DNA into the transformed cell DNA. Acquisition of viral DNA by the transformed cell is thought to lead to malignant transformation. Mouse mammary tumors are also induced by genetically inherited MMTV proviral genes. We examined the DNA of 16 genetically induced C3H mouse mammary carcinomas for rearrangement or reintegration of MMTV proviral genes by restriction endonuclease digestion and Southern blot analysis. Amplification of endogenous MMTV DNA in these tumors by reintegration was rare. Despite this all the tumors were expressing viral genes as measured by radioimmune competition assay, immunoperoxidase and electron microscopy. Examination of tumor DNA after digestion with methysensitive HpaII restriction endonuclease showed that proviral DNA was hypomethylated, i.e. associated with transcriptionally active DNA. Therefore, mammary tumorigenesis by MMTV may occur in the absence of MMTV DNA reintegration and transformation of mammary epithelium may instead be mediated through direct expression of viral gene products or alternatively by the expression of a virus gene product-induced cellular gene.